The long-term objectives of this proposal are to investigate the phenomena of degeneration, repair, and regeneration in the mammalian cochlea. Understanding degeneration is important for determining mechanisms of damage with the aim of preventing certain types of cochlear injury. Knowledge about the processes of repair may provide a biological means for limiting cochlear damage after an ototraumatic insult. Information on the newly discovered phenomenon of neural regeneration may provide future hope for restoration of destroyed cochlear tissues in severely hearing-impaired individuals. Degeneration will be examined in studies involving: the continuity of the reticular lamina using in-vivo perfusion of extracellular tracer particles; pathological changes in the bodies and peripheral processes of the spiral ganglion cells using a combined organ of Corti/modiolus dissection technique; and quantitative determination of the age-related changes in the cochlea under ambient and reduced noise conditions. Repair will be examined in studies involving phagocytosis of cellular debris and its relation to the formation of scars in the organ of Corti using a technique to label phagocytic white blood cells prior to damaging the cochlea. The neural regeneration studies will involve determining: the origin of the regenerated nerve fibers using acetylcholinesterase staining and fiber tracing techniques; the location and morphological appearance of the fiber terminals; and the persistence and the magnitude of the regeneration response as a function of age at the time of injury. Noise exposure or "natural" aging will be used as tools to damage the ears of groups of chinchillas. After variable survival times, their cochleas will be prepared for examination by phase-contrast microscopy as plastic- embedded whole mounts so that the pattern and base-to-apex location of pathological changes can be accurately determined. Selected regions of these specimens will then be sectioned for transmission electron microscopic study. In some binaurally exposed animals, the amount of cellular damage or the magnitude of neural regeneration will be statistically compared in their right and left ears. This will permit the delineation of some of the factors (local, systemic, genetic) responsible for the phenomena of degeneration, repair and regeneration.